Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Ciclopirox Ethanolamine Preserves the Immature State of Human HSCs by Mediating Intracellular Iron Content

Safaee Talkhoncheh, Mehrnaz LU ; Baudet, Aurélie LU ; Ek, Fredrik LU ; Subramaniam, Agatheeswaran LU ; Kao, Yun-Ruei ; Miharada, Natsumi LU ; Karlsson, Christine LU ; Oburoglu, Leal LU orcid ; Rydström, Anna LU and Žemaitis, Kristijonas LU , et al. (2023) In Blood Advances 7(24). p.7407-7417
Abstract

Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. To elucidate regulatory mechanisms governing the maintenance and propagation of human HSCs ex vivo, we screened libraries of annotated small molecules in human cord blood (CB) cells using an optimized assay for detection of functional HSCs during culture. We found that the antifungal agent ciclopirox ethanolamine (CPX) selectively supported immature CD34+CD90+ cells during culture and enhanced their long-term in vivo repopulation capacity. Purified HSCs treated with CPX showed a reduced cell division rate and an enrichment of HSC- specific gene expression patterns. Mechanistically, we found that the HSC stimulating... (More)

Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. To elucidate regulatory mechanisms governing the maintenance and propagation of human HSCs ex vivo, we screened libraries of annotated small molecules in human cord blood (CB) cells using an optimized assay for detection of functional HSCs during culture. We found that the antifungal agent ciclopirox ethanolamine (CPX) selectively supported immature CD34+CD90+ cells during culture and enhanced their long-term in vivo repopulation capacity. Purified HSCs treated with CPX showed a reduced cell division rate and an enrichment of HSC- specific gene expression patterns. Mechanistically, we found that the HSC stimulating effect of CPX was directly mediated by chelation of the intracellular iron pool, which in turn affected iron-dependent proteins and enzymes mediating cellular metabolism and respiration. Our findings unveil a significant impact of iron homeostasis in regulation of human HSCs, with important implications for both basic HSC biology and clinical hematology.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood Advances
volume
7
issue
24
pages
7407 - 7417
publisher
American Society of Hematology
external identifiers
  • scopus:85181044148
  • pmid:37487020
ISSN
2473-9529
DOI
10.1182/bloodadvances.2023009844
language
English
LU publication?
yes
additional info
Copyright © 2023 American Society of Hematology.
id
caee1641-aed6-4db3-9fb0-58c1bddf11fa
date added to LUP
2023-09-01 08:43:47
date last changed
2024-04-21 23:38:36
@article{caee1641-aed6-4db3-9fb0-58c1bddf11fa,
  abstract     = {{<p>Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. To elucidate regulatory mechanisms governing the maintenance and propagation of human HSCs ex vivo, we screened libraries of annotated small molecules in human cord blood (CB) cells using an optimized assay for detection of functional HSCs during culture. We found that the antifungal agent ciclopirox ethanolamine (CPX) selectively supported immature CD34+CD90+ cells during culture and enhanced their long-term in vivo repopulation capacity. Purified HSCs treated with CPX showed a reduced cell division rate and an enrichment of HSC- specific gene expression patterns. Mechanistically, we found that the HSC stimulating effect of CPX was directly mediated by chelation of the intracellular iron pool, which in turn affected iron-dependent proteins and enzymes mediating cellular metabolism and respiration. Our findings unveil a significant impact of iron homeostasis in regulation of human HSCs, with important implications for both basic HSC biology and clinical hematology.</p>}},
  author       = {{Safaee Talkhoncheh, Mehrnaz and Baudet, Aurélie and Ek, Fredrik and Subramaniam, Agatheeswaran and Kao, Yun-Ruei and Miharada, Natsumi and Karlsson, Christine and Oburoglu, Leal and Rydström, Anna and Žemaitis, Kristijonas and Alattar, Abdul Ghani and Rak, Justyna and Pietras, Kristian and Olsson, Roger and Will, Britta and Larsson, Jonas}},
  issn         = {{2473-9529}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{24}},
  pages        = {{7407--7417}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood Advances}},
  title        = {{Ciclopirox Ethanolamine Preserves the Immature State of Human HSCs by Mediating Intracellular Iron Content}},
  url          = {{http://dx.doi.org/10.1182/bloodadvances.2023009844}},
  doi          = {{10.1182/bloodadvances.2023009844}},
  volume       = {{7}},
  year         = {{2023}},
}